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Influenza polymerase

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https://www.readbyqxmd.com/read/28719323/burden-and-seasonality-of-viral-acute-respiratory-tract-infections-among-outpatients-in-southern-sri-lanka
#1
David Shapiro, Champica K Bodinayake, Ajith Nagahawatte, Vasantha Devasiri, Ruvini Kurukulasooriya, Jeremy Hsiang, Bradley Nicholson, Aruna Dharshan De Silva, Truls Østbye, Megan E Reller, Christopher W Woods, L Gayani Tillekeratne
In tropical and subtropical settings, the epidemiology of viral acute respiratory tract infections varies widely between countries. We determined the etiology, seasonality, and clinical presentation of viral acute respiratory tract infections among outpatients in southern Sri Lanka. From March 2013 to January 2015, we enrolled outpatients presenting with influenza-like illness (ILI). Nasal/nasopharyngeal samples were tested in duplicate using antigen-based rapid influenza testing and multiplex polymerase chain reaction (PCR) for respiratory viruses...
July 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28717324/investigation-of-avian-influenza-infection-in-wild-birds-in-ismailia-and-damietta-cities-egypt
#2
Hanaa Mohamed Fadel, Rabab Afifi
AIM: This study was carried out to monitor avian influenza (AI) infection in wild birds in Egypt. MATERIALS AND METHODS: A total of 135 wild birds were examined for the presence of H5, H7, and H9 hemagglutination inhibition antibodies. Organs and swab samples of 75 birds were screened by multiplex real-time reverse transcriptase-polymerase chain reaction (RRT-PCR) to detect AI subtypes H5, H7, and H9 matrix genes. RESULTS: The highest seropositive result was recorded in cattle egrets (90...
June 2017: Veterinary World
https://www.readbyqxmd.com/read/28709841/characterization-of-susceptibility-variants-of-poliovirus-grown-in-the-presence-of-favipiravir
#3
Tohru Daikoku, Mineyuki Mizuguchi, Takayuki Obita, Takeshi Yokoyama, Yoshihiro Yoshida, Masaya Takemoto, Kimiyasu Shiraki
BACKGROUND: T-705 (favipiravir) is a potent inhibitor of RNA-dependent RNA polymerases of influenza viruses and no favipiravir-resistant virus has been isolated. Poliovirus RNA polymerase has been well characterized and isolation of resistant virus was examined in poliovirus. METHODS: Susceptibility variants of poliovirus I (Sabin strain) were isolated during passages in the presence of favipiravir and characterized for their susceptibility and the sequence of RNA polymerase...
June 29, 2017: Journal of Microbiology, Immunology, and Infection, Wei Mian Yu Gan Ran za Zhi
https://www.readbyqxmd.com/read/28676793/immune-responses-of-chickens-infected-with-wild-bird-origin-h5n6-avian-influenza-virus
#4
Shimin Gao, Yinfeng Kang, Runyu Yuan, Haili Ma, Bin Xiang, Zhaoxiong Wang, Xu Dai, Fumin Wang, Jiajie Xiao, Ming Liao, Tao Ren
Since April 2014, new infections of H5N6 avian influenza virus (AIV) in humans and domestic poultry have caused considerable economic losses in the poultry industry and posed an enormous threat to human health worldwide. In previous research using gene sequence and phylogenetic analysis, we reported that H5N6 AIV isolated in February 2015 (ZH283) in Pallas's sandgrouse was highly similar to that isolated in a human in December 2015 (A/Guangdong/ZQ874/2015), whereas a virus (i.e., SW8) isolated in oriental magpie-robin in 2014 was highly similar to that of A/chicken/Dongguan/2690/2013 (H5N6)...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/28666191/exploring-the-cycloheptathiophene-3-carboxamide-scaffold-to-disrupt-the-interactions-of-the-influenza-polymerase-subunits-and-obtain-potent-anti-influenza-activity
#5
Jenny Desantis, Giulio Nannetti, Serena Massari, Maria Letizia Barreca, Giuseppe Manfroni, Violetta Cecchetti, Giorgio Palù, Laura Goracci, Arianna Loregian, Oriana Tabarrini
With the aim to identify small molecules able to disrupt PA-PB1 subunits interaction of influenza virus (flu) RNA-dependent RNA polymerase, and based on previous structural and computational information, in this paper we have designed and synthesized a new series of cycloheptathiophene-3-carboxamide (cHTC) derivatives. Their biological evaluation led to highlight important structural insights along with new interesting compounds, such as the 2-hydroxybenzamido derivatives 29, 31, and 32, and the 4-aminophenyl derivative 54, which inhibited viral growth in the low micromolar range (EC50 = 0...
June 8, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28664296/rapid-virulence-shift-of-an-h5n2-avian-influenza-virus-during-a-single-passage-in-mice
#6
Jeong-Hyun Nam, Sang-Mu Shim, Eun-Jung Song, Erica Españo, Dae-Gwin Jeong, Daesub Song, Jeong-Ki Kim
Influenza A viruses must undergo adaptation to acquire virulence in new host species. In mouse models, host adaptation for virulence is generally performed through 5 to 20 lung-to-lung passages. However, highly pathogenic avian influenza viruses (e.g., H5N1 and H7N7 subtypes) have been observed to acquire virulence in mice after only a few in vivo passages. In this study, a low-pathogenic avian influenza H5N2 virus, A/Aquatic Bird/Korea/CN2/2009, which was a prevalent subtype in South Korea in 2009, was serially passaged in mice to evaluate its potential to become highly pathogenic...
June 29, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28656006/clinical-characteristics-of-influenza-associated-pneumonia-of-adults-clinical-features-and-factors-contributing-to-severity-and-mortality
#7
Takashi Ishiguro, Naho Kagiyama, Ryuji Uozumi, Kyuto Odashima, Yotaro Takaku, Kazuyoshi Kurashima, Satoshi Morita, Noboru Takayanagi
Background: Pneumonia is a major complication of influenza that contributes to mortality. Clinical characteristics and factors of influenza virus contributing to the severity and mortality of pneumonia have not been fully elucidated. Objective: The objective was to clarify clinical characteristics and factors contributing to the severity and mortality of influenza-associated pneumonia (flu-p). Methods: We retrospectively analyzed patients with flu-p. Results: From December 1999 to March 2016, 210 patients with a median age of 69 (range, 17 to 92) years with flu-p based on positive rapid antigen tests, increased antibody titers of paired sera, or positive results of reverse transcription polymerase chain reaction were admitted to our institution...
June 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28652020/development-of-a-realtime-rt-pcr-assay-for-the-rapid-detection-of-influenza-a-h2-viruses
#8
Komissarov Andrey, Fadeev Artem, Kosheleva Anna, Grudinin Mikhail
Influenza and other acute respiratory infections are of great concern for public health, causing excessive morbidity and mortality throughout the world. Influenza virus A(H2N2), which caused a pandemic of so called "Asian flu" in 1957 was expelled from the human population by the new pandemic virus subtype H3N2 in 1968, however, influenza A(H2) viruses continue to circulate in wild birds and poultry. The lack of immunity in human population and the continued circulation of influenza A(H2) among animals makes emergence of a new pandemic virus possible...
June 23, 2017: Molecular and Cellular Probes
https://www.readbyqxmd.com/read/28646802/dampness-can-promote-the-influenza-a-virus-and-worsen-its-prognosis-by-upregulating-the-tlr7-signaling-pathway
#9
Deng Li, Xu Huachong, Pang Peng, Zheng Ke, Nie Jiao, Wu Xianlin, Yu Bin, Chen Jia, Chen Xiaoyin
Context • Outbreaks of the influenza A virus (IAV) are increasingly recognized as a global public health issue, affecting a large proportion of the world's population. A number of studies have provided epidemiologic evidence that dampness and mold are consistently associated with multiple allergic and respiratory effects, but they focused on dampness-related pathogenic microorganisms leading to allergy rather than the dampness itself. Objective • The current study intended to examine the effects of a damp environment on the promotion of the IAV and determine the adverse effects on its prognosis through upregulation of the toll-like receptor 7 (TLR7)-signaling pathway in the lung...
June 23, 2017: Alternative Therapies in Health and Medicine
https://www.readbyqxmd.com/read/28646652/influenza-a-virus-cap-snatches-host-rnas-based-on-their-abundance-early-after-infection
#10
Dorota Sikora, Lynda Rocheleau, Earl G Brown, Martin Pelchat
The influenza A virus RNA polymerase cleaves the 5' ends of host RNAs and uses these RNA fragments as primers for viral mRNA synthesis. We performed deep sequencing of the 5' host-derived ends of the eight viral mRNAs of influenza A/Puerto Rico/8/1934 (H1N1) virus in infected A549 cells, and compared the population to those of A/Hong Kong/1/1968 (H3N2) and A/WSN/1933 (H1N1). In the three strains, the viral RNAs target different populations of host RNAs. Host RNAs are cap-snatched based on their abundance, and we found that RNAs encoding proteins involved in metabolism are overrepresented in the cap-snatched populations...
June 21, 2017: Virology
https://www.readbyqxmd.com/read/28639594/viral-aetiology-of-wheezing-in-children-under-five
#11
Prithi Sureka Mummidi, Radha Tripathy, Bhagirathi Dwibedi, Amarendra Mahapatra, Suryakanta Baraha
BACKGROUND & OBJECTIVES: Wheezing is a common problem in children under five with acute respiratory infections (ARIs). Viruses are known to be responsible for a considerable proportion of ARIs in children. This study was undertaken to know the viral aetiology of wheezing among the children less than five years of age, admitted to a tertiary care hospital in eastern India. METHODS: Seventy five children, under the age of five years admitted with wheezing, were included in the study...
February 2017: Indian Journal of Medical Research
https://www.readbyqxmd.com/read/28637755/seasonal-h3n2-and-2009-pandemic-h1n1-influenza-a-viruses-reassort-efficiently-but-produce-attenuated-progeny
#12
Kara L Phipps, Nicolle Marshall, Hui Tao, Shamika Danzy, Nina Onuoha, John Steel, Anice C Lowen
Reassortment of gene segments between co-infecting influenza A viruses (IAV) facilitates viral diversification and has significant epidemiological impact on seasonal and pandemic influenza. Since 1977, human IAVs of H1N1 and H3N2 subtypes have co-circulated with relatively few documented cases of reassortment. We evaluated the potential for viruses of the 2009 pandemic H1N1 (pH1N1) and seasonal H3N2 lineages to reassort under experimental conditions. Results of heterologous co-infections with pH1N1 and H3N2 viruses were compared to those obtained following co-infection with homologous, genetically tagged, pH1N1 viruses as a control...
June 21, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28636855/efficacy-of-recombinant-influenza-vaccine-in-adults-50-years-of-age-or-older
#13
RANDOMIZED CONTROLLED TRIAL
Lisa M Dunkle, Ruvim Izikson, Peter Patriarca, Karen L Goldenthal, Derek Muse, Janice Callahan, Manon M J Cox
BACKGROUND: Improved influenza vaccines are needed to control seasonal epidemics. This trial compared the protective efficacy in older adults of a quadrivalent, recombinant influenza vaccine (RIV4) with a standard-dose, egg-grown, quadrivalent, inactivated influenza vaccine (IIV4) during the A/H3N2-predominant 2014-2015 influenza season, when antigenic mismatch between circulating and vaccine influenza strains resulted in the reduced effectiveness of many licensed vaccines. METHODS: We conducted a randomized, double-blind, multicenter trial of RIV4 (45 μg of recombinant hemagglutinin [HA] per strain, 180 μg of protein per dose) versus standard-dose IIV4 (15 μg of HA per strain, 60 μg of protein per dose) to compare the relative vaccine efficacy against reverse-transcriptase polymerase-chain-reaction (RT-PCR)-confirmed, protocol-defined, influenza-like illness caused by any influenza strain starting 14 days or more after vaccination in adults who were 50 years of age or older...
June 22, 2017: New England Journal of Medicine
https://www.readbyqxmd.com/read/28631174/studies-of-the-interaction-of-influenza-virus-rna-polymerase-pan-with-endonuclease-inhibitors
#14
Li-Hua Dong, Xiao-Rong Cao
Influenza virus is a major causative agent of respiratory viral infections, and RNA polymerase catalyzes its replication and transcription activities in infected cell nuclei. Since it is highly conserved in all virus strains, RNA polymerase becomes a key target of anti-influenza virus agents. Although experimental studies have revealed the good inhibitory activity of endonuclease inhibitors to RNA polymerase, the mechanism is still unclear. In this study, the docking and molecular dynamics simulations have been performed to explore the interaction of three kinds of endonuclease inhibitors with the subunit (PAN) of RNA polymerase...
June 19, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/28629986/identification-of-influenza-polymerase-inhibitors-targeting-polymerase-pb2-cap-binding-domain-through-virtual-screening
#15
Ming Liu, Chun-Yeung Lo, Guoxin Wang, Hak-Fun Chow, Jacky Chi-Ki Ngo, David Chi-Cheong Wan, Leo Lit-Man Poon, Pang-Chui Shaw
Influenza A virus is the major cause of epidemics and pandemics worldwide. In this study, virtual screening was used to identify compounds interacting with influenza A polymerase PB2 cap-binding domain (CBD). With a database of 21,351 small molecules, 28 candidate compounds were tested and one compound (225) was identified as hit compound. Compound 225 and three of its analogs (225D1, 426 and 426Br) were found to bind directly to PB2 CBD by surface plasmon resonance (SPR). The evaluation of compounds 426Br and 225 indicated that they could bind to PB2 CBD and inhibit influenza virus at low micromolar concentration...
June 16, 2017: Antiviral Research
https://www.readbyqxmd.com/read/28629724/in%C3%A2-vitro-antiviral-effects-of-peganum-harmala-seed-extract-and-its-total-alkaloids-against-influenza-virus
#16
Mohammad-Taghi Moradi, Ali Karimi, Mahmoud Rafieian-Kopaei, Fatemeh Fotouhi
This research was aimed to evaluate the in vitro antiviral effect and the mechanism of the effect of Peganum. harmala seeds extract against influenza A virus infection using Madin-Darby canine kidney (MDCK) cells. In this research, ethyl alcohol extract of P. harmala seeds and its total alkaloids was prepared. The potential antiviral activity of the extract and its total alkaloids against influenza A/Puerto Rico/8/34 (H1N1; PR8) virus was assessed. The mode of action of the extract to inhibit influenza replication was investigated using virucidal activity, hemagglutination inhibition assay, time of addition assays, RNA replication, western blot analysis and RNA polymerase blocking assay...
June 16, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28628827/evolutionary-conservation-of-influenza-a-pb2-sequences-reveals-potential-target-sites-for-small-molecule-inhibitors
#17
Hershna Patel, Andreas Kukol
The influenza A basic polymerase protein 2 (PB2) functions as part of a heterotrimer to replicate the viral RNA genome. To investigate novel PB2 antiviral target sites, this work identified evolutionary conserved regions across the PB2 protein sequence amongst all sub-types and hosts, as well as ligand binding hot spots which overlap with highly conserved areas. Fifteen binding sites were predicted in different PB2 domains; some of which reside in areas of unknown function. Virtual screening of ~50,000 drug-like compounds showed binding affinities of up to -10...
June 16, 2017: Virology
https://www.readbyqxmd.com/read/28627657/shrna%C3%A2-mediated-np-knockdown-inhibits-the-apoptosis-of-cardiomyocytes-induced-by-h1n1pdm2009-influenza-virus
#18
Kun Yu, Yi Ren, Xiwen Zhang, Taiping Qiao, Zhiguo Liu, Jianhua Shi, Yingnan Wang
Acute influenza-associated myocarditis varies in clinical severity ranging between asymptomatic and fulminant varieties. The most severe cases can result in impaired cardiac function‑associated mortality; however, the mechanism underlying the development of viral myocarditis has yet to be fully elucidated. The present study investigated the apoptosis induced in H9C2 cardiomyocytes by infection with the H1N1pdm2009 virus. The H9C2 cells were transfected with nucleoprotein (NP)‑specific short hairpin (sh) RNA, and viral replication was re‑evaluated in H9C2 cells infected with the H1N1pdm2009 virus, as was the apoptosis induced by the virus...
August 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28622865/pa-x-protein-decreases-replication-and-pathogenicity-of-swine-influenza-virus-in-cultured-cells-and-mouse-models
#19
Xiao-Qian Gong, Ying-Feng Sun, Bao-Yang Ruan, Xiao-Min Liu, Qi Wang, Hai-Ming Yang, Shuai-Yong Wang, Peng Zhang, Xiu-Hui Wang, Tong-Ling Shan, Wu Tong, Yan-Jun Zhou, Guo-Xin Li, Hao Zheng, Guang-Zhi Tong, Hai Yu
Swine influenza viruses have been circulating in pigs throughout world and might be potential threats to human health. PA-X protein is a newly discovered protein produced from the PA gene by ribosomal frameshifting and the effects of PA-X on the 1918 H1N1, the pandemic 2009 H1N1, the highly pathogenic avian H5N1 and the avian H9N2 influenza viruses have been reported. However, the role of PA-X in the pathogenesis of swine influenza virus is still unknown. In this study, we rescued the H1N1 wild-type (WT) classical swine influenza virus (A/Swine/Guangdong/1/2011 (H1N1)) and H1N1 PA-X deficient virus containing mutations at the frameshift motif, and compared their replication properties and pathogenicity of swine influenza virus in vitro and in vivo...
June 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28622854/linear-dna-vaccine-prepared-by-large-scale-pcr-provides-protective-immunity-against-h1n1-influenza-virus-infection-in-mice
#20
Fei Wang, Quanjiao Chen, Shuntang Li, Chenyao Zhang, Shanshan Li, Min Liu, Kun Mei, Chunhua Li, Lixin Ma, Xiaolan Yu
Linear DNA vaccines provide effective vaccination. However, their application is limited by high cost and small scale of the conventional polymerase chain reaction (PCR) generally used to obtain sufficient amounts of DNA effective against epidemic diseases. In this study, a two-step, large-scale PCR was established using a low-cost DNA polymerase, RKOD, expressed in Pichia pastoris. Two linear DNA vaccines encoding influenza H1N1 hemagglutinin (HA) 1, LEC-HA, and PTO-LEC-HA (with phosphorothioate-modified primers), were produced by the two-step PCR...
June 2017: Veterinary Microbiology
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